ACP InternistWeekly

In the News for the Week of July 16, 2013

Highlights

Side effects rare with statins, two types may have best safety profiles

Side effects associated with statin therapy are not common, and simvastatin and pravastatin may be safer and more tolerable
than other drugs in the class, reported a meta-analysis that totaled nearly a quarter-million people. More...

Long-term use of alternate-day, low-dose aspirin may reduce risk for colorectal cancer but increase risk for gastrointestinal
bleeding in healthy women, a new study found. More...

Test yourself

MKSAP Quiz: 4-week history of wheals and burning sensation without pruritus

A 27-year-old woman is evaluated for a 4-week history of wheals, characterized by a burning sensation without pruritus. Each
individual lesion persists for 48 hours and slowly resolves, leaving a bruise. Current medications are diphenhydramine, hydroxyzine,
cetirizine and oral contraceptives. Following a physical exam, what is the most appropriate management? More...

Diabetes

Telmisartan and valsartan associated with fewer hospital admissions than other ARBs, study finds

In patients with diabetes, telmisartan and valsartan were associated with lower rates of hospitalization for cardiovascular
events than other angiotensin-receptor blockers (ARBs), according to a recent retrospective study. More...

Breast cancer

Updated guideline released on chemoprevention for breast cancer

The American Society of Clinical Oncology (ASCO) released a clinical practice guideline last week on pharmacologic interventions
for reducing breast cancer risk. More...

Pneumonia

New childhood vaccine dropped hospitalizations in elderly, too

U.S. hospitalizations for pneumonia declined substantially, especially among children and the elderly, after introduction
of the 7-valent pneumococcal conjugant vaccine (PCV7), according to a new study. More...

From the College

ACP releases annual report from the Executive Vice President

The 2012-2013 ACP Report of the Executive Vice President (EVP) is now available on ACP's website. More...

Governance Committee seeks Regent candidates for 2014

The Governance Committee oversees the process for nominating and electing Masters and Fellows of the College to the Board
of Regents (BOR) and is beginning the process of seeking Regents to join the Board in May 2014. More...

Vote for your favorite entry

Highlights

Side effects rare with statins, two types may have best safety profiles

Side effects associated with statin therapy are not common, and simvastatin and pravastatin may be safer and more tolerable
than other drugs in the class, reported a meta-analysis that totaled nearly a quarter-million people.

Researchers systematically reviewed 55 two-armed placebo-controlled trials and 80 two- or multiarmed active-comparator trials
that enrolled 246,955 individuals with and without cardiovascular disease to evaluate different statins. Results were published by Circulation: Cardiovascular Quality and Outcomes on July 9.

Individual statins showed no significant differences from controls for the following side effects :

Statins as a class resulted in significantly higher odds of diabetes (OR, 1.09; 95% CI, 1.02 to 1.16) and transaminase elevations
(OR, 1.51; 95% CI, 1.24 to 1.84) compared with controls. However, there was no evidence of increased risk of cancer among
100,523 participants (OR, 0.96; 95% credible interval, 0.91 to 1.02; I2, 0.0%), nor was there evidence of potential head-to-head differences between statins for these outcomes.

The researchers noted that when statins were compared, there were numerous statistically detectable differences favoring simvastatin
and pravastatin. Dose-level comparisons showed there were higher odds of discontinuations with higher doses of atorvastatin
and rosuvastatin, while higher doses of atorvastatin, fluvastatin, lovastatin and simvastatin were associated with higher
odds of transaminase elevations. Simvastatin at its highest doses was associated with creatine kinase elevations (OR, 4.14;
95% credible interval, 1.08 to 16.24).

The researchers wrote, "At the population level, mortality and cardiovascular benefits of statin therapy greatly overweigh
its potential harms, even taking into account the recent finding that statin use is associated with a modest increase in diabetes
mellitus incidence. At the individual level, however, there may be a risk of exposing a large group of individuals to the
(primarily minor) harms of statin therapy for the benefit of a smaller number of individuals. This brings into sharp focus
the importance of correctly identifying the set of individuals who stand to benefit from statin therapy."

Long-term use of alternate-day, low-dose aspirin may reduce risk for colorectal cancer but increase risk for gastrointestinal
bleeding in healthy women, a new study found.

Researchers followed 39,876 women aged 45 years or older in the Women's Health Study (WHS) who took 100 mg of alternate-day
aspirin or placebo beginning April 30, 1993, through Jan. 24, 1996 and ending March 31, 2004. There was a median of 10 years
of follow-up among 33,682 women through March 2012.

The researchers noted that delayed differences in cancer outcomes by aspirin assignment may indicate an effect in the early
stages of carcinogenesis, requiring a long latent period, especially at low doses, or that increased gastrointestinal bleeding
leads to more endoscopy and early polyp removal.

They wrote, "However, rates of colonoscopy or sigmoidoscopy were similar among groups in the WHS, and we found no difference
in reported colon polyp occurrence over time. Furthermore, the greatest effect was seen in the proximal colon, which is less
affected by sigmoidoscopy. Even if reduced cancer is caused by increased endoscopy and polyp removal due to symptoms, the
net clinical effect seems to be a reduction in colorectal cancer."

Test yourself

MKSAP Quiz: 4-week history of wheals and burning sensation without pruritus

A 27-year-old woman is evaluated for a 4-week history of wheals, characterized by a burning sensation without pruritus. Each
individual lesion persists for 48 hours and slowly resolves, leaving a bruise. Current medications are diphenhydramine, hydroxyzine,
cetirizine and oral contraceptives. The patient's mother has systemic lupus erythematosus.

On physical examination, vital signs are normal. She has scattered edematous indurated erythematous plaques consistent with
wheals. There are scattered ecchymoses at the sites of fading lesions. The patient has no facial lesions or rash, and her
mucous membranes are normal. There is no joint swelling or tenderness.

Diabetes

Telmisartan and valsartan associated with fewer hospital admissions than other ARBs, study finds

In patients with diabetes, telmisartan and valsartan were associated with lower rates of hospitalization for cardiovascular
events than other angiotensin-receptor blockers (ARBs), according to a recent retrospective study.

The population-based cohort study included about 54,000 Ontario residents over age 65 who had type 2 diabetes and started
treatment with telmisartan, valsartan, candesartan, irbesartan or losartan between 2001 and 2011. The primary outcome was
a composite of hospital admission for acute myocardial infarction, stroke or heart failure. Results were published by CMAJ on July 8.

After multivariable adjustment, patients taking telmisartan or valsartan had a lower risk of the primary outcome than those
on irbesartan (adjusted hazard ratio [HR] for telmisartan, 0.85 [95% CI, 0.74 to 0.97]; HR for valsartan, 0.86 [95% CI, 0.77
to 0.95]). There were no significant differences in the primary outcome among the other ARBs. The researchers also found a
reduction specifically in hospitalizations for heart failure with telmisartan compared to irbesartan (HR, 0.79 [95% CI, 0.66
to 0.96]).

The observed advantages of telmisartan may be due to its activation of the PPARγ receptor, the study authors speculated.
The benefit found for valsartan is harder to explain and was attenuated by adjustment for dose, but it may be related to inhibition
of platelet aggregation, they wrote. The study was limited by its observational nature, but many variables were controlled
for and a randomized trial of all these agents is unlikely, so the authors concluded telmisartan and valsartan may be the
preferred ARBs for older patients with diabetes. The results are not necessarily applicable to younger patients or those without
diabetes, they noted.

An accompanying editorial expressed doubts about the authors' conclusions, arguing that PPARγ agonism would not lead to the cardiovascular benefit
seen in the study and that there was no likely explanation for the observed advantage of valsartan. The results are intriguing,
the editorialist wrote, but "there is scant evidence to support preferring one drug in this class over another for patients with type 2 diabetes."

Breast cancer

Updated guideline released on chemoprevention for breast cancer

The American Society of Clinical Oncology (ASCO) released a clinical practice guideline last week on pharmacologic interventions
for reducing breast cancer risk.

The guideline updates the 2009 guideline on this topic and was developed based on a systematic review of 19 randomized, controlled
trials and meta-analyses published from June 2007 through June 2012. Six drugs were considered: the selective estrogen-receptor
modulators tamoxifen, raloxifene, arzoxifene and lasofoxifene and the aromatase inhibitors exemestane and anastrozole.

An update committee involving experts in clinical medicine, public health, clinical research, health services and related
areas, plus a patient representative, reviewed the evidence and drafted the recommendations, which were then peer reviewed
and reviewed and approved by the ASCO Clinical Practice Guidelines Committee. The guideline addresses only chemoprevention
and does not consider survival or lifestyle interventions. It was published online July 8 by the Journal of Clinical Oncology.

The guideline recommendations include the following:

In women at least 35 years of age who are at increased risk for breast cancer or have lobular carcinoma in situ, oral tamoxifen
(20 mg/d for five years) should be discussed as an option to reduce the risk of estrogen receptor-positive disease. Tamoxifen
is not recommended in women with a history of deep venous thrombosis, pulmonary embolism, stroke or transient ischemic attack.
It is also not recommended in women undergoing prolonged immobilization; in women who are pregnant, may be become pregnant
or are nursing; or in women taking hormone therapy.

In postmenopausal women who are at increased risk for breast cancer or have lobular carcinoma in situ, oral raloxifene (60
mg/d for five years) should be discussed as an option to reduce risk for estrogen receptor-positive disease. Raloxifene is
not recommended in premenopausal women; in women with a history of deep venous thrombosis, pulmonary embolism, stroke or transient
ischemic attack; or in women undergoing prolonged immobilization.

Oral exemestane (25 mg/d for five years) should also be discussed as an alternative to tamoxifen or raloxifene to reduce risk
of estrogen receptor-positive disease in postmenopausal women who are at increased risk for breast cancer, who have lobular
carcinoma in situ, or who have atypical hyperplasia. It is not recommended for breast cancer risk reduction in premenopausal
women. The guideline noted that exemestane is currently FDA-approved only for adjuvant treatment of early breast cancer and
treatment of advanced breast cancer.

Increased risk was defined as a five-year projected absolute risk of 1.66% or greater (based on the National Cancer Institute
Breast Cancer Risk Assessment Tool or an equivalent measure) or a diagnosis of lobular carcinoma in situ. The guideline does
not recommend using other selective estrogen-receptor modulators or aromatase inhibitors to lower breast cancer risk outside
a clinical trial setting. Of note, fenretinide is no longer included in the 2013 guideline update because the update committee
considered it no longer relevant for breast cancer chemoprevention.

Clinicians are encouraged to discuss the option of chemoprevention with women at increased breast cancer risk, the guideline
said, including the specific risks and benefits associated with each prospective agent.

Pneumonia

New childhood vaccine dropped hospitalizations in elderly, too

U.S. hospitalizations for pneumonia declined substantially, especially among children and the elderly, after introduction
of the 7-valent pneumococcal conjugant vaccine (PCV7), according to a new study.

Researchers compared estimated annual rates of hospitalization for pneumonia in 1997-1999 and 2007-2009 using diagnoses from
the Nationwide Inpatient Sample database. Hospitalizations were included if pneumonia was the first listed diagnosis or a
secondary diagnosis after sepsis, meningitis or empyema. PCV7 was introduced into the U.S. childhood immunization schedule
in 2000. Results were published in the July 11 New England Journal of Medicine.

Compared to 1997-1999, annual hospitalizations for pneumonia in children under 2 years in 2007-2009 dropped by 551.1 per 100,000
(95% CI, 445.1 to 657.1), which researchers extrapolated to 47,000 avoided hospitalizations annually. Patients age 85 and
over saw an even greater decrease, of 1300.8 per 100,000 (95% CI, 984.0 to 1617.6) or 73,000 fewer hospitalizations annually.
Reductions in hospitalizations were also seen in patients 18 to 39 years, 65 to 74 years and 75 to 84 years (8.4, 85.3 and
359.8 per 100,000 respectively). Overall, researchers calculated an annual reduction in pneumonia hospitalizations of 168,000
per year.

Previous research had shown that introduction of PCV7 rapidly reduced pneumonia hospitalizations among children, but there
was concern that other serotypes would increase correspondingly to erode this progress, the study authors noted. This study
shows that the success in reducing hospitalizations was maintained through 2009 and that the vaccine also had a significant
effect on unvaccinated age groups, which is perhaps more remarkable than its success in young children, the authors said.

Although the results could be confounded by changes in coding practices, hospital admission thresholds and other factors,
studies from other countries, which also found drops in pneumonia hospitalizations after PCV7 introduction, support a causal
association. International studies have also shown that a substantial proportion of adult pneumonia cases are still attributable
to the serotypes in the vaccine. It is uncertain whether adult vaccination with PCV13 (which contains the seven serotypes
included in PCV7 and was recently recommended for immunocompromised adults in the U.S.) will add to the indirect benefits
observed in this study and reduce adult pneumonia hospitalizations further, the authors concluded.

From the College

ACP releases annual report from the Executive Vice President

The 2012-2013 ACP Report of the Executive Vice President (EVP) is now available on ACP's website. The annual report provides brief summaries of the new products, programs and services
produced during the past fiscal year. Enhancing the summaries are photos, graphic images, and embedded links that direct viewers
to more detailed sources of information.

The 2012-2013 report highlights ACP activities in four areas—knowledge, leadership, practice support and collaboration.
The report also features a letter to ACP members and a short video with a recorded message from EVP and CEO Steven Weinberger,
MD, FACP.

As part of ACP's ongoing effort to be environmentally responsible and reduce the use of paper, the report has been produced
in a digital format that is accessible from all mobile devices. A tabbed menu and scrolling feature make it easy to move around
the report, view content, and locate specific topics of interest.

Governance Committee seeks Regent candidates for 2014

The Governance Committee oversees the process for nominating and electing Masters and Fellows of the College to the Board
of Regents (BOR) and is beginning the process of seeking Regents to join the Board in May 2014.

The Governance Committee oversees the process for nominating and electing Masters and Fellows of the College to the Board
of Regents (BOR) and is beginning the process of seeking Regents to join the Board in May 2014.

The Governance Committee will strive to represent the diversity within internal medicine on ACP's Board of Regents. Important
general qualifications include commitment to ACP, dependability, leadership qualities, and the ability to represent the College
in numerous and diverse arenas. Regent nominees must be Fellows or Masters of the College.

All candidates for Regent must submit a letter of nomination (not from the candidate) and two letters of support (from two
individuals other than the nominator) by Aug. 1, 2013.

Letters of nomination should include the following sections:

brief description of the nominee's current activities,

special attributes the candidate would bring to the BOR in terms of the desired characteristics outlined above,

previous and current service in College-related activities,

service in organizations other than the College (medical and nonmedical) and

identification of two individuals who will write letters of support for the candidate.

Letters of support do not need to have specific content or format but will be most useful if they focus on the candidate's
qualifications and how he or she would contribute to the BOR and the College.

MKSAP Answer and Critique

The correct answer is C: Skin biopsy. This item is available to MKSAP 16 subscribers as item 14 in the Dermatology
section. More information is available online.

This patient has atypical urticaria, and the diagnostic test of choice is skin biopsy to evaluate for the presence of vasculitis.
Her individual lesions last longer than a few hours and are not pruritic. The presence of burning, tingling, or painful wheals
is unusual for simple urticaria. Lesions that last for more than 24 hours and resolve with bruising are concerning for urticarial
vasculitis. Approximately 50% of patients with urticarial vasculitis have an underlying autoimmune disease such as systemic
lupus erythematosus.

Many medications may trigger urticaria. Oral contraceptives can cause urticarial eruptions, including chronic urticaria, typically
through progesterone exposure. This frequently manifests as a cyclic urticaria. Urticarial vasculitis is less frequently caused
by medications and has not been associated with oral contraceptives.

Patients with a clear food or environmental trigger for urticarial eruptions may benefit from radioallergosorbent (RAST) testing;
however, this patient is presenting with atypical urticarial lesions with signs and symptoms concerning for urticarial vasculitis.
RAST testing plays no role in the diagnosis of urticarial vasculitis.

Thyroid function testing is indicated in the evaluation of chronic urticaria, in which patients have regular episodes of urticaria
over a period of more than 6 weeks. Given the atypical presentation of this patient's wheals and the lack of historical features
or physical examination findings consistent with thyroid disease, testing is not indicated at this time.

Key Point

Lesions that persist for more than 24 hours and resolve with bruising should be biopsied to evaluate for urticarial vasculitis.

Test yourself

A 66-year-old man is evaluated for a persistent rash for 6 years' duration. The rash waxes and wanes in severity, and it becomes pruritic only after he becomes hot and sweating, such as when he mows the lawn or exercises. It has always been limited to his back and lower chest. He has never treated it. The patient is otherwise well, has no other medical problems, and takes no medication. Following a physical exam, what is the most likely diagnosis?

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